Electrical Impedance Spectroscopy As a Tool to Detect the Epithelial to Mesenchymal Transition in Prostate Cancer Cells

Overview

Journal Biosensors (Basel)

Specialty Biotechnology

Date 2024 Oct 25

PMID 39451716

Authors

Lexi L C Simpkins

Luis A Henriquez

Mary Tran

Tayloria N G Adams

Affiliations

Soon will be listed here.

Abstract

Prostate cancer (PCa) remains a significant health threat, with chemoresistance and recurrence posing major challenges despite advances in treatment. The epithelial to mesenchymal transition (EMT), a biochemical process where cells lose epithelial features and gain mesenchymal traits, is linked to chemoresistance and metastasis. Electrical impedance spectroscopy (EIS), a novel label-free electrokinetic technique, offers promise in detecting cell phenotype changes. In this study, we employed EIS to detect EMT in prostate cancer cells (PCCs). PC3, DU145, and LNCaP cells were treated with EMT induction media for five days. EIS characterization revealed unique impedance spectra correlating with metastatic potential, distinguishing DU145 EMT+ and EMT- cells, and LNCaP EMT+ and EMT- cells (in combination with dielectrophoresis), with comparisons made to epithelial and mesenchymal controls. These changes were supported by shifts in electrical signatures, morphologies, and protein expression, including the downregulation of E-cadherin and upregulation of vimentin. No phenotype change was observed in PC3 cells, which maintained a mesenchymal phenotype. EMT+ cells were also distinguishable from mixtures of EMT+ and EMT- cells. This study demonstrates key advancements: the application of EIS and dielectrophoresis for label-free EMT detection in PCCs, characterization of cell electrical signatures after EMT, and EIS sensitivity to EMT transitions. Detecting EMT in PCa is important to the development of more effective treatments and overcoming the challenges of chemoresistance.

References

Hubner Y, Hoettges K, Kass G, Ogin S, Hughes M . Parallel measurements of drug actions on Erythrocytes by dielectrophoresis, using a three-dimensional electrode design. IEE Proc Nanobiotechnol. 2006; 152(4):150-4. DOI: 10.1049/ip-nbt:20050011. View

Kalluri R, Weinberg R . The basics of epithelial-mesenchymal transition. J Clin Invest. 2009; 119(6):1420-8. PMC: 2689101. DOI: 10.1172/JCI39104. View

Wei X, Xiong H, Zhou Y, Chen X, Yang W . Tracking epithelial-mesenchymal transition in breast cancer cells based on a multiplex electrochemical immunosensor. Biosens Bioelectron. 2024; 258:116372. DOI: 10.1016/j.bios.2024.116372. View

KAIGHN M, Narayan K, Ohnuki Y, Lechner J, Jones L . Establishment and characterization of a human prostatic carcinoma cell line (PC-3). Invest Urol. 1979; 17(1):16-23. View

Moya L, Walpole C, Rae F, Srinivasan S, Seim I, Lai J . Characterisation of cell lines derived from prostate cancer patients with localised disease. Prostate Cancer Prostatic Dis. 2023; 26(3):614-624. PMC: 10449630. DOI: 10.1038/s41391-023-00679-x. View

Teixeira V, Barth T, Labitzky V, Schumacher U, Krautschneider W . Electrical Impedance Spectroscopy for Characterization of Prostate PC-3 and DU 145 Cancer Cells. Annu Int Conf IEEE Eng Med Biol Soc. 2020; 2019:6485-6489. DOI: 10.1109/EMBC.2019.8856627. View

Hoettges K, Henslee E, Torcal Serrano R, Jabr R, Abdallat R, Beale A . Ten-Second Electrophysiology: Evaluation of the 3DEP Platform for high-speed, high-accuracy cell analysis. Sci Rep. 2019; 9(1):19153. PMC: 6915758. DOI: 10.1038/s41598-019-55579-9. View

Hildebrandt C, Buth H, Cho S, Impidjati , Thielecke H . Detection of the osteogenic differentiation of mesenchymal stem cells in 2D and 3D cultures by electrochemical impedance spectroscopy. J Biotechnol. 2010; 148(1):83-90. DOI: 10.1016/j.jbiotec.2010.01.007. View

Rudzinski J, Govindasamy N, Lewis J, Jurasz P . The role of the androgen receptor in prostate cancer-induced platelet aggregation and platelet-induced invasion. J Thromb Haemost. 2020; 18(11):2976-2986. DOI: 10.1111/jth.15020. View

10.

Bagnaninchi P, Drummond N . Real-time label-free monitoring of adipose-derived stem cell differentiation with electric cell-substrate impedance sensing. Proc Natl Acad Sci U S A. 2011; 108(16):6462-7. PMC: 3080969. DOI: 10.1073/pnas.1018260108. View

11.

Adams T, Jiang A, Mendoza N, Ro C, Lee D, Lee A . Label-free enrichment of fate-biased human neural stem and progenitor cells. Biosens Bioelectron. 2020; 152:111982. PMC: 8860404. DOI: 10.1016/j.bios.2019.111982. View

12.

Simon M, Li Y, Arulmoli J, McDonnell L, Akil A, Nourse J . Increasing label-free stem cell sorting capacity to reach transplantation-scale throughput. Biomicrofluidics. 2015; 8(6):064106. PMC: 4240779. DOI: 10.1063/1.4902371. View

13.

Buczek M, Miles A, Green W, JOHNSON C, Boocock D, Pockley A . Cytoplasmic PML promotes TGF-β-associated epithelial-mesenchymal transition and invasion in prostate cancer. Oncogene. 2015; 35(26):3465-75. PMC: 4932557. DOI: 10.1038/onc.2015.409. View

14.

Horoszewicz J, Leong S, Kawinski E, Karr J, Rosenthal H, Chu T . LNCaP model of human prostatic carcinoma. Cancer Res. 1983; 43(4):1809-18. View

15.

Papanikolaou S, Vourda A, Syggelos S, Gyftopoulos K . Cell Plasticity and Prostate Cancer: The Role of Epithelial-Mesenchymal Transition in Tumor Progression, Invasion, Metastasis and Cancer Therapy Resistance. Cancers (Basel). 2021; 13(11). PMC: 8199975. DOI: 10.3390/cancers13112795. View

16.

Wei J, Wu X, Li Y, Tao X, Wang B, Yin G . Identification of Potential Predictor of Biochemical Recurrence in Prostate Cancer. Int J Gen Med. 2022; 15:4897-4905. PMC: 9113455. DOI: 10.2147/IJGM.S355435. View

17.

De Ninno A, Reale R, Giovinazzo A, Bertani F, Businaro L, Bisegna P . High-throughput label-free characterization of viable, necrotic and apoptotic human lymphoma cells in a coplanar-electrode microfluidic impedance chip. Biosens Bioelectron. 2019; 150:111887. DOI: 10.1016/j.bios.2019.111887. View

18.

Du B, Shim J . Targeting Epithelial-Mesenchymal Transition (EMT) to Overcome Drug Resistance in Cancer. Molecules. 2016; 21(7). PMC: 6273543. DOI: 10.3390/molecules21070965. View

19.

Giaever I, Keese C . Micromotion of mammalian cells measured electrically. Proc Natl Acad Sci U S A. 1991; 88(17):7896-900. PMC: 52411. DOI: 10.1073/pnas.88.17.7896. View

20.

Cruz M, Siden A, Calaf G, Delwar Z, Yakisich J . The stemness phenotype model. ISRN Oncol. 2012; 2012:392647. PMC: 3423925. DOI: 10.5402/2012/392647. View